Cytomegalovirus (CMV) Infection among Pediatric Patients

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (15 October 2024) | Viewed by 5316

Special Issue Editors


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Department of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Interests: neonatal infections; surveillance; prevention and treatment; neonatal immunology
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Guest Editor
1. Research Area, Management Innovations and Clinical Pathways, Bambino Gesu’ Children’s Hospital, IRCCS, Rome, Italy
2. Fac Med & Surg, Microbiol Immunol Infect Dis & Transplants MIMIT, University of Rome, Tor Vergata, Rome, Italy
Interests: children; pediatrics; pediatric immunology

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Guest Editor
Research Area, Management Innovations and Clinical Pathways, Bambino Gesu’ Children’s Hospital, IRCCS, Rome, Italy
Interests: children; pediatrics; pediatric immunology

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Guest Editor
Research Area, Management Innovations and Clinical Pathways, Bambino Gesu’ Children’s Hospital, IRCCS, Rome, Italy
Interests: children; pediatrics; pediatric immunology

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Guest Editor
Research Area, Management Innovations and Clinical Pathways, Bambino Gesu’ Children’s Hospital, IRCCS, Rome, Italy
Interests: pregnancy and viral infections

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Guest Editor
Section of Neonatology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, 1200 Bruxelles, Belgium
Interests: infections in neonates
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cytomegalovirus (CMV) is a member of the herpesvirus family (Herpesviridae), which is highly widespread worldwide. It is estimated that the prevalence is particularly high in countries with a low level of economic development, where the prevalence in women of reproductive age can reach 85–100%. Children are particularly susceptible to CMV infections, and the prevalence rates among them reach 30% within the first five years of life. In general, CMV seroprevalence is higher among women, those in older age groups, people of low socioeconomic status, and in developing countries (1). Once contracted for the first time (primary infection), the virus remains latent in the body and the reactivation of the latent virus or infection with a different strain of CMV can occur at every stage of life (non-primary infection). The CMV infection of greatest concern is that contracted by a pregnant woman. The virus crosses the placenta with a different probability depending on the order of the infection: in primary infection, the probability of transmission ranges from 35 to 70%, and in the reactivation of the latent infection, it ranges from 0.5 to 1.5%. Fetal damage resulting from the transmission of the virus is of different intensity depending on the woman's gestational period. Today, drugs that can be administered both in pregnancy and in the first year of life are available that seem to prevent both maternal-fetal transmission of the virus and serious damage to the fetus/neonate. Therefore, the possibility of an early and accurate diagnosis in pregnancy and after birth represents a pre-requisite for the prevention of the outcomes of these maternal infections on the newborn and on the child. In this Special Issue, we intend to deal with the diagnosis of first infections and reinfections in pregnancy, the possible feto-neonatal outcomes, the usefulness of universal newborn screening, hearing outcomes in the child, radiological diagnostics, and the type and duration of therapies.

Dr. Cinzia Auriti
Dr. Domenico Umberto De Rose
Dr. Iliana Bersani
Dr. Francesca Campi
Dr. Maria Paola Ronchetti
Prof. Dr. Fiammetta Piersigilli
Guest Editors

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Keywords

  • congenital cytomegalovirus infections
  • cytomegalovirus
  • cytomegalovirus in pregnancy
  • newborns
  • sensory neural hearing loss
  • long-term outcomes

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Published Papers (4 papers)

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Research

10 pages, 471 KiB  
Article
Cytomegalovirus-Specific Hyperimmune Immunoglobulin Administration for Secondary Prevention after First-Trimester Maternal Primary Infection: A 13-Year Single-Center Cohort Study
by Emmanouil Karofylakis, Konstantinos Thomas, Dimitra Kavatha, Lamprini Galani, Sotirios Tsiodras, Helen Giamarellou, Vassiliki Papaevangelou and Anastasia Antoniadou
Viruses 2024, 16(8), 1241; https://doi.org/10.3390/v16081241 - 2 Aug 2024
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Abstract
Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. [...] Read more.
Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55–13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection among Pediatric Patients)
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18 pages, 12941 KiB  
Article
Characterization of Natural Killer Cell Profile in a Cohort of Infected Pregnant Women and Their Babies and Its Relation to CMV Transmission
by Chiara Pighi, Arianna Rotili, Maia De Luca, Sara Chiurchiù, Francesca Ippolita Calò Carducci, Chiara Rossetti, Loredana Cifaldi, Roberto Bei, Leonardo Caforio, Stefania Bernardi, Paolo Palma and Donato Amodio
Viruses 2024, 16(5), 780; https://doi.org/10.3390/v16050780 - 14 May 2024
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Abstract
Human cytomegalovirus (CMV) is a common herpesvirus causing lifelong latent infection in most people and is a primary cause of congenital infection worldwide. Given the role of NK cells in the materno-fetal barrier, we investigated peripheral blood NK cell behavior in the context [...] Read more.
Human cytomegalovirus (CMV) is a common herpesvirus causing lifelong latent infection in most people and is a primary cause of congenital infection worldwide. Given the role of NK cells in the materno-fetal barrier, we investigated peripheral blood NK cell behavior in the context of CMV infection acquired during pregnancy. We analyzed the NK phenotype and CD107a surface mobilization on PBMCs from CMV-transmitting and non-transmitting mothers and newborns with or without congenital infection. NK cells from non-transmitting mothers showed the typical phenotype of CMV-adaptive NK cells, characterized by higher levels of NKG2C, CD57, and KIRs, with reduced NKG2A, compared to transmitting ones. A significantly higher percentage of DNAM-1+, PD-1+, and KIR+NKG2A-CD57+PD-1+ CD56dim cells was found in the non-transmitting group. Accordingly, NK cells from congenital-CMV (cCMV)-infected newborns expressed higher levels of NKG2C and CD57, with reduced NKG2A, compared to non-congenital ones. Furthermore, they showed a significant expansion of CD56dim cells co-expressing NKG2C and CD57 or with a memory-like (KIR+NKG2A-CD57+NKG2C+) phenotype, as well as a significant reduction of the CD57-NKG2C- population. Degranulation assays showed a slightly higher CD107a geomean ratio in NK cells of mothers who were non-transmitting compared to those transmitting the virus. Our findings demonstrate that both CMV-transmitting mothers and cCMV newborns show a specific NK profile. These data can guide studies on predicting virus transmission from mothers and congenital infection in infants. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection among Pediatric Patients)
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12 pages, 1099 KiB  
Article
Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?
by Giannina Izquierdo, Carolina Guerra, Roberto Reyes, Leslie Araya, Belén Sepulveda, Camila Cabrera, Pamela Medina, Eledier Mardones, Leonel Villavicencio, Luisa Montecinos, Felipe Tarque, William Acevedo, Marlon Barraza, Mauricio Farfán, Jocelyn Mendez and Juan Pablo Torres
Viruses 2024, 16(5), 772; https://doi.org/10.3390/v16050772 - 13 May 2024
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Abstract
Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated [...] Read more.
Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. Methods: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. Results: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22–0.84), with significantly higher rates (2.1%, 95% CI 0.58–5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31–4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23–37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). Conclusions: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection among Pediatric Patients)
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11 pages, 1975 KiB  
Article
Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
by Songpon Getsuwan, Nopporn Apiwattanakul, Chatmanee Lertudomphonwanit, Suradej Hongeng, Sophida Boonsathorn, Wiparat Manuyakorn, Pornthep Tanpowpong, Usanarat Anurathapan, Kanchana Tangnararatchakit and Suporn Treepongkaruna
Viruses 2023, 15(11), 2213; https://doi.org/10.3390/v15112213 - 4 Nov 2023
Viewed by 1485
Abstract
Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection [...] Read more.
Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4–12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = −0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation. Full article
(This article belongs to the Special Issue Cytomegalovirus (CMV) Infection among Pediatric Patients)
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